Former mayor Thomas M. Menino has been diagnosed months after leaving office with an advanced form of cancer that has spread to his liver and lymph nodes, a jolting discovery that he described as the most profound challenge of his life.

Menino has never been one to hide his feelings, not the joy he felt at governing his city for a record 20 years, not the agony over retiring from the job he loved. But as he sat in his elaborately paneled university office Friday in a quiet corner of Boston, he concealed his emotions with a steady determination.

His doctors described in a separate interview an advanced cancer of unknown origin that had metastasized. Despite an exhaustive search, doctors said they have been unable to find the source of the cancer and suggested they never will. It was discovered in early February as his primary care physician, Dr. Charles A. Morris, examined Menino’s back because of chronic weakness in his legs.

“They did a scan and Morris called me and said, ‘You have to come see me.’ He was more shaken up than I was,” Menino said.

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The 71-year-old former mayor, who endured a succession of serious ailments in 2012, began an intravenous chemotherapy regimen in early March at Dana-Farber Cancer Institute, which he said he handled relatively well. He said he is expected to have three more chemo sessions, at two-week intervals. His doctors said surgery is not currently a treatment option. He falls in what his oncologist described as the 3 or 4 percent of cancer patients whose disease cannot be pinpointed.

Sitting at his desk at Boston University, framed by a bay window with sweeping views of the frozen Charles River two stories below, Menino was at turns defiant and philosophical, though always resolute.

“My attitude really is, we’ll get through it,” Menino said. “We got through the [illnesses in 2012], we’ll get through this. I have great doctors and supportive friends.”

“What else can you do?” he asked. “What I don’t want is people feeling sorry for me. I don’t want sympathy. There are people worse off than me. It’s my biggest concern — I don’t want to be treated any differently.”

Next week, he is scheduled to go to Rochester, N.Y., for a speech. In early April, it’s New Orleans. Menino delivered a speech in New York at the Council on Foreign Relations after his diagnosis, as well as at Saint Anselm College in New Hampshire, and he visited Red Sox spring training in Florida last week.

On one of his trips, Menino got in an argument with an airport security agent who wanted to take his cane, which is shaped like a Louisville Slugger.

The cancer had no connection to Menino’s cascade of medical struggles in the last few years, his doctors said. In late 2012, he fell gravely ill on a vacation in Italy. He was initially diagnosed with a respiratory infection and a blood clot. While hospitalized, he suffered a compression fracture in a vertebra and was later diagnosed with type 2 diabetes. Menino spent eight weeks in Boston hospitals.

“I’m confident that during that stay there was no evidence of the cancer,” Morris said.

His oncologist, Dr. Charles S. Fuchs, said he reviewed all of Menino’s previous X-rays and other high-tech medical scans. “There was absolutely no evidence of this,” Fuchs said.

‘What I don’t want is people feeling sorry for me. I don’t want sympathy.’

“It is an advanced cancer of unknown primary origin,” Fuchs said. “At diagnosis, you do an exhaustive search [for the primary cancer], which we’ve done. In these sorts of circumstances, candidly, it is unlikely you will find the source in our experience.”

The new diagnosis is also unrelated to Menino’s two previous bouts with cancer, his doctors said. In 2003, he underwent two surgeries to remove a rare form of cancer between his shoulder blades. Two years ago, he had minor surgery to remove a cancerous growth from his nose. It was basal cell carcinoma, the most common type of skin cancer.

“There would be no connection between this and his other medical problems,” Morris said. “And no connection with his medical issues that were publicly discussed over the course of the last year.”

Menino has not felt any pain or discomfort from the new cancer, he said. Before the diagnosis, there were no indications that something was wrong.

“Even in retrospect, there is nothing we can point to that would suggest early symptoms,” Morris said. “His team truly feels this was an incidental discovery working up and evaluating an unrelated issue.”

The initial round of chemotherapy went well.

“Our goal is that this therapy will prove effective,” Fuchs said. “How it will work, and what the expectations are, we really can’t speak to, recognizing that every patient is different.”

Menino — who on Friday wore a starched white shirt, his signature City of Boston pen peeking from the pocket — has been confronted by this challenge as he grappled with the adjustment from City Hall to the halls of academia, where he is helping launch an Institute on Cities at BU.

“It’s different, much different — going from a hectic schedule to a university schedule,” Menino said without hesitation. “You don’t use the word ‘meeting.’ You say ‘convene.’ ”

He sat Friday surrounded by the aspects of his new life. He stole glances at an Apple computer on his desk and occasionally announced the arrival of a new e-mail. Menino picked up his new iPhone and demonstrated his skill playing a game called “Candy Crush” introduced to him by a grandson.

On his desk, spread out in front of him, was the nearly completed manuscript to a memoir that he co-wrote with author Jack Beatty, to be published by Houghton Mifflin Harcourt in September.

Menino has kept busy with Thursday office hours for students, planning a symposium on the Boston Marathon bombings for late March, and an appearance at BU by US Senator Elizabeth Warren.

Does he miss the mayoralty? He smiled wanly.

“A lot,” Menino said. “I drive down the street and see something — why isn’t that done! I come around the corner toward my house and I still look for the police officer who was always parked in front.”

But Menino said he made a decision and is at peace. He knew he could not keep the frenetic pace of his old schedule. “You need to be in the neighborhoods all the time,” Menino said. “That’s what a mayor is supposed to do, keep the pulse of the community.”

The cancer diagnosis came just weeks into his new job at BU. He acknowledged his surprise, but remained determined.

“We’ll get there,” Menino said. “I don’t worry about it. I have no control over it.”

After four chemotherapy treatments, Menino said his doctors will examine his progress. “I’m confident,” he said. “I feel great. And I’m not faking it.”

His wife, Angela, continues to be his deepest reservoir of support.

“She’s a strong kid,” Menino said. “I don’t worry about me. I worry about my family. I can take it.” He paused and added, softer now, “I can take it.”

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